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- Title
Post-transfer editing mechanism of a D-aminoacyl-tRNA deacylase-like domain in threonyl-tRNA synthetase from archaea.
- Authors
Hussain, Tanweer; Kruparani, Shobha P.; Pal, Biswajit; Dock-Bregeon, Anne-Catherine; Dwivedi, Shweta; Shekar, Megala R.; Sureshbabu, Kotini; Sankaranarayanan, Rajan
- Abstract
To ensure a high fidelity during translation, threonyl-tRNA synthetases (ThrRSs) harbor an editing domain that removes noncognate L-serine attached to tRNAThr. Most archaeal ThrRSs possess a unique editing domain structurally similar to D-aminoacyl-tRNA deacylases (DTDs) found in eubacteria and eukaryotes that specifically removes D-amino acids attached to tRNA. Here, we provide mechanistic insights into the removal of noncognate L-serine from tRNAThr by a DTD-like editing module from Pyrococcus abyssi ThrRS (Pab-NTD). High-resolution crystal structures of Pab-NTD with pre- and post-transfer substrate analogs and with L-serine show mutually nonoverlapping binding sites for the seryl moiety. Although the pre-transfer editing is excluded, the analysis reveals the importance of main chain atoms in proper positioning of the post-transfer substrate for its hydrolysis. A single residue has been shown to play a pivotal role in the inversion of enantioselectivity both in Pab-NTD and DTD. The study identifies an enantioselectivity checkpoint that filters opposite chiral molecules and thus provides a fascinating example of how nature has subtly engineered this domain for the selection of chiral molecules during translation.
- Subjects
MOLECULAR biology; ENZYMES; PROTEIN synthesis; ARCHAEBACTERIA; ENANTIOSELECTIVE catalysis
- Publication
EMBO Journal, 2006, Vol 25, Issue 17, p4152
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601278